The toxicokinetics of pentachloroanisole (PCA) was studies in F344 rats and B6C3F1 mice of both sexes at doses of 10, 20 and 40 mg/Kg. A rapid elimination of PCA and a rapid formation of pentachlorophenol (PCP) was observed in both species after an iv or an oral dose of PCA. No sex differences were found in the rate of absorption of PCA from the GI tract or in the overall rate of elimination of PCA. The estimated area under concentration versus time curves (AUC) of PCA after gavage or iv administration is similar for both sexes and both species. However, the AUC of metabolite (PCP) was significantly larger in female rats than in male rats at all gavage doses. No difference was observed in mice. The AUC of PCA increased disproportionally with dose in both species. The results of these studies indicate that the observed sex differences of rats and mice in toxic and carcinogenic response to PCA is not related to the systemic availability of PCA or to the rate of demethylation of PCA to PCP. The high plasma concentrations and relatively long biological half-life of PCP in both species after iv and oral dosing with PCA indicates that bioaccumulation of PCP will occur upon multiple oral administration of PCA.